JP6436142B2 - Image processing apparatus and method, and program - Google Patents

Description

  The present disclosure relates to an image processing apparatus and method, and a program, and more particularly, to an image processing apparatus and method, and a program that enable easy and non-invasive observation of pulsation propagation.

  In the field of regenerative medicine, the use of cultured cells produced by culturing cells is used to regenerate body cells, tissues, organs, etc. lost due to accidents or illness, and to restore their functions. ing. There are a wide variety of cell tissues that can be produced as such cultured cells, and one of them is a cardiomyocyte, which is used for the treatment of the heart. This cultured cardiomyocyte itself moves corresponding to a pulsation. Therefore, in the production stage of cultured cardiomyocytes, it is necessary to evaluate the quality of whether the above movement is good, for example.

  In evaluating the quality of such cultured cardiomyocytes, for example, in the present situation, visual observation is performed. In addition, the potential is measured by inserting an electrode into a cultured cardiomyocyte. However, visual observation is largely dependent on the subjectivity of the observer, and it is difficult to obtain an objective and accurate evaluation result. Further, when measuring the potential, there is a problem that the electrode is in contact with the cultured cardiomyocytes and is not non-invasive. Further, information that can be quantified based on the measurement by the potential is limited to, for example, about the pulsation time. Furthermore, the measurement object is limited on the electrode.

  Therefore, as a conventional technique, a measurement point is set in an imaging screen obtained by photographing cardiomyocytes, and the luminance of the measurement point is automatically measured, and the deformation period of the cardiomyocytes is measured from the measurement value. Is known (see, for example, Patent Document 1).

  By the way, pulsations in various regions obtained by analyzing a phase difference observation moving image of cultured cardiomyocytes show cooperative pulsations depending on the number of culture days, but show fluctuations due to administration of various drugs. By detecting such fluctuations by some method, it becomes possible to evaluate in advance the drug toxicity, effects and the like at the time of drug discovery.

  Conventionally, for example, there has been a method of detecting an external field potential of a cell with an electrode arranged on the bottom of a culture dish and capturing a pulsation behavior of the cell by a change in the membrane potential of the cell. In addition, a fluorescent dye that emits light by binding to calcium is inserted into the cell, and the pulsation rhythm of the cell is detected by detecting the calcium concentration that fluctuates due to the excitation (action potential) of the cell. There was also a way to evaluate the pattern.

JP-A-63-233392 (FIG. 1)

  However, in the case of a method in which an electrode is placed on a culture dish and a potential change is detected, a specific culture dish is required. In addition, since the propagation detection of pulsations depends on the density of the electrodes placed on the culture dish, it is difficult to detect a complicated propagation pattern with the density of the existing apparatus. Further, in the case of the method of inserting the fluorescent dye, the fluorescent dye is expensive, and the operation of inserting the fluorescent dye is complicated and takes time, and there is a risk of fading. Furthermore, in these methods, since a voltage is applied to the observation target or a fluorescent dye is introduced, the observation target may be affected. That is, with these methods, there is a possibility that observation of pulsation cannot be easily and noninvasively performed.

  This indication is made in view of such a situation, and it aims at enabling propagation of pulsation to be observed easily and noninvasively.

One aspect of the present disclosure, the generation unit determines a motion amount or direction of cardiomyocytes in each partial area of the viewing area, to produce a distribution of the motion amount or direction of the myocardial cells of each of the partial region determined An image processing apparatus is provided.

The generation unit can display a distribution regarding the amount or direction of movement of the cardiomyocytes for each of the determined partial regions.
The generation unit can display a frequency distribution of the amount or direction of movement of the cardiomyocytes for each determined partial region.

The generator can make displaying the distribution before and after drug administration.

An evaluation unit that evaluates propagation of movement of the cardiomyocytes based on the change in the distribution can be further provided.
The evaluation unit can evaluate a change in the distribution before and after drug administration.

The evaluation unit can evaluate the toxicity or effect of the administered drug.
The evaluation unit can evaluate the propagation of heartbeat pulsations.

  The partial area may constitute the whole or a part of the observation area.

The generation unit can display a distribution regarding the amount and direction of movement of the cardiomyocytes for each of the determined partial regions.

A motion detector that detects the motion of the cardiomyocytes for each partial region of the observation region; and a motion calculator that calculates the amount or direction of the motion of the cardiomyocytes detected by the motion detector. Can be.

The movement detection unit detects the motion of each frame of the moving image of the heart muscle cells, the motion calculation unit may calculate the motion amount or direction for each frame of the moving image of the heart muscle cells.

One aspect of the present disclosure also determines an amount of motion or direction of cardiomyocytes for each partial region of the observation region and generates a distribution of the determined amount of cardiac muscle cells for each partial region or direction. It is a processing method.

One aspect of the present disclosure further computer, to determine the motion amount or direction of cardiomyocytes in each partial area of the viewing area, the distribution of the motion amount or direction of the myocardial cells of each of the partial region determined It is a program for making it function as a production | generation part to produce | generate.

In one aspect of the present disclosure, the amount of movement or direction of cardiomyocytes is determined for each partial region of the observation region, and a distribution of the amount of movement or direction of cardiomyocytes for each determined partial region is generated.

  According to the present disclosure, an image can be processed. In particular, propagation of pulsation can be observed easily and non-invasively.

It is a figure explaining the cooperation of a motion. It is a figure explaining the cooperation of a motion. It is a block diagram which shows the main structural examples of a chemical | medical agent evaluation apparatus. It is the figure which imaged the example of the mode of the influence on propagation of pulsation by medicine administration. It is the figure which imaged other examples of the mode of influence on propagation of pulsation by medicine administration. It is the figure which imaged another example of the mode of the influence on propagation of pulsation by medicine administration. It is a block diagram which shows the main structural examples of an evaluation parameter | index data generation part. It is a figure explaining the structural example of evaluation object image data. It is a block diagram which shows the main structural examples of a motion detection part. It is a figure explaining the example of the block division of frame image data. It is a figure explaining the structural example of motion detection data. It is a block diagram which shows the main structural examples of an evaluation part. It is a block diagram which shows the main structural examples of a motion evaluation part. It is a figure explaining the example of the mode of motion amount gravity center evaluation. It is a figure explaining the example of the mode of correlation histogram evaluation. It is a figure following FIG. 15 explaining the example of the mode of correlation histogram evaluation. It is a figure following FIG. 16 explaining the example of the mode of correlation histogram evaluation. It is a flowchart explaining the example of the flow of an evaluation process. It is a flowchart explaining the example of the flow of an evaluation parameter | index data generation process. It is a flowchart explaining the example of the flow of an impact evaluation process. It is a flowchart explaining the example of the flow of a motion evaluation process. FIG. 26 is a block diagram illustrating a main configuration example of a personal computer.

Hereinafter, modes for carrying out the present disclosure (hereinafter referred to as embodiments) will be described. The description will be made in the following order.
1. First embodiment (drug evaluation apparatus)
2. Second embodiment (personal computer)

<1. First Embodiment>
[Cultivated cardiomyocytes]
For example, in regenerative medicine, various human tissues and organs are treated using cultured cells that are cell tissues produced by culturing cells collected from a living body. A cultured cell 1 shown in FIG. 1A is obtained by culturing and growing cardiomyocytes. Cultured cardiomyocytes, which are cultured cells obtained by culturing cardiomyocytes, may be used, for example, for heart treatment. It is also used for evaluating toxicity to the heart in drug discovery.

  In vivo, cardiomyocytes pulsate constantly repeating contraction and relaxation. Therefore, the cultured cell 1 which is a cultured cardiomyocyte also moves in a predetermined direction as shown by a motion vector 2 shown in FIG. 1B so that the whole of the cultured cell 1 repeatedly contracts and relaxes. Actually, a cardiomyocyte has a part that beats autonomously and a part that beats depending on surrounding beats. That is, depending on the site, the cultured cell 1 may not autonomously beat. In such a case, the cultured cell 1 can be beaten by periodically applying a voltage from the outside to the cultured cell 1 using an electrode. Thus, the pulsation of the cultured cell 1 pace-made by applying an external voltage is basically the same as the case of autonomous pulsation. That is, even when the cultured cell 1 pulsates autonomously or when it pulsates due to voltage application, it can be similarly observed using the present technology.

  FIG. 1C divides the observation area of the cultured cell 1 into a plurality of partial areas (blocks), detects the amount of movement (motion vector) for each block, and observes the temporal transition thereof. For example, a graph 4-1 in FIG. 1C shows a temporal transition of the motion amount of the block 3-1, and a graph 4-2 shows a temporal transition of the motion amount of the block 3-2. .

  Graphs 5-1 to 5-3 in FIG. 2A show the amount of cell movement in block 3-1 shown in graph 4-1 and the amount of cell movement in block 3-2 shown in graph 4-2. It shows the temporal transition of the relationship.

  The amount of cell movement initially present in the block 3-1 and the amount of cell movement present in the block 3-2 are low in correlation with each other as shown in the graph 5-1, when collected from the living body. It is. However, as time passes and the culture progresses, the correlation between the two gradually increases as shown in graph 5-2, and as time passes, the correlation between the two increases as shown in graph 5-3. Sex is very strong.

  That is, as in the graph shown in FIG. 2B, the correlation coefficient of the amount of movement between the plurality of positions of the grown cultured cell 1 is stabilized at a large value. That is, the cooperativity of the movement of cells in each region is strengthened. Ideally, the movements of the cells are related to each other, and the entire cultured cell 1 is pulsated as one living tissue.

  The grown cultured cell 1 is composed of a plurality of cells, and signals are transmitted between the cells via gap junctions. Thereby, a correlation arises in a motion between cells, and the whole cultured cell 1 comes to beat as one biological tissue. In cultured cells 1 grown in this way, pulsations propagate between the cells.

  The cultured cells 1j having such a high correlation (cooperativity) and propagation of pulsation can be used for drug evaluation. For example, by administering a drug to the cultured cell 1 and observing the movement before and after that, the effect and toxicity of the drug can be evaluated from the change in the movement of the cultured cell 1.

[Drug evaluation device]
FIG. 3 is a block diagram illustrating a main configuration example of the medicine evaluation apparatus.

  The drug evaluation apparatus 100 shown in FIG. 3 is an apparatus that evaluates a drug administered to the cultured cardiomyocytes 110 by observing the movement of the cultured cardiomyocytes 110. As illustrated in FIG. 3, the medicine evaluation apparatus 100 includes an imaging unit 101, an evaluation target image data generation recording unit 102, an evaluation index data generation unit 103, and an evaluation unit 104.

  The imaging unit 101 images the cultured cardiomyocytes 110 to be observed. The imaging unit 101 may image the cultured cardiomyocytes 110 directly (without passing through other members), or may image the cultured cardiomyocytes 110 through other members such as a microscope.

  Moreover, the cultured cardiomyocytes 110 may be fixed with respect to the imaging unit 101 or may not be fixed. In general, it is desirable that the cultured cardiomyocytes 110 are fixed to the imaging unit 101 in order for the drug evaluation apparatus 100 to detect movement (temporal change in position).

  The imaging unit 101 images the cultured cardiomyocytes 110 for a predetermined period. That is, the imaging unit 101 obtains a moving image with the cultured cardiomyocytes 110 as a subject. The imaging unit 101 images the cultured cardiomyocytes 110 before and after drug administration. Note that the imaging unit 101 may image the cultured cardiomyocytes 110 a plurality of times after drug administration, for example, according to a predetermined condition such as every predetermined time.

  The imaging unit 101 supplies an image signal 111 (moving image) of an image of the cultured cardiomyocytes 110 obtained by imaging to the evaluation target image data generation / recording unit 102.

  The evaluation target image data generation / recording unit 102 generates evaluation target image data based on the image signal supplied from the imaging unit 101, and records and stores the generated evaluation target image data in, for example, an internal recording medium. The evaluation object image data generated here is, for example, moving image data generated from an image signal obtained by imaging the cultured cardiomyocytes 110.

  For example, the evaluation target image data generation / recording unit 102 may extract only a part of the frame images from a plurality of frame images supplied from the imaging unit 101 and use them as evaluation target image data. Good. Further, for example, the evaluation target image data generation / recording unit 102 extracts a partial region of each frame image supplied from the imaging unit 101 as a small frame image, and a moving image including the small frame image is determined as the evaluation target image data. You may make it.

  Further, for example, the evaluation target image data generation / recording unit 102 may perform arbitrary image processing on each frame image supplied from the imaging unit 101, and the image processing result may be used as evaluation target image data. . As the image processing, for example, image enlargement, reduction, rotation, deformation, brightness and chromaticity correction, sharpness, noise removal, intermediate frame image generation, and the like can be considered. Of course, any image processing other than these may be used.

  The evaluation target image data generation recording unit 102 supplies the stored evaluation target image data 112 to the evaluation index data generation unit 103 at a predetermined timing or based on a request from the evaluation index data generation unit 103.

  The evaluation index data generation unit 103 observes each block, which is a partial region obtained by dividing the entire region of the image of the observation target (cultured cardiomyocytes 110) into a plurality of frames between the frame images of the supplied evaluation target image data 112. The motion of the target (cultured cardiomyocytes 110) is detected.

  The evaluation index data generation unit 103 represents the detected motion of each block as a motion vector, and obtains the magnitude (motion amount) of the motion vector. Since the amount of movement is an absolute value, this amount of movement is also referred to as a movement amount absolute value in the following.

  The evaluation index data generation unit 103 supplies the motion amount absolute value to the evaluation unit 104 as evaluation index data 113.

  The evaluation unit 104 maps the absolute value of the amount of motion supplied as the evaluation index data 113 to a two-dimensional color map, expresses the state of pulsation propagation, and further evaluates the state quantitatively. The drug is evaluated. The evaluation unit 104 outputs the two-dimensional color map and the quantitative evaluation result as an evaluation value 114.

  The two-dimensional color map represents the size of a parameter at each position on a plane with a color. In this case, the plane represents the observation area of the cultured cardiomyocytes 110, and the color represents the absolute value of movement (the magnitude of the value). That is, the position of the motion amount absolute value is represented by a position on the plane, and the magnitude of the value is represented by a color. That is, the distribution of the absolute value of the motion amount in the observation area is indicated by the change of the color on the plane.

  Examples of such a two-dimensional color map are shown in FIGS. Each of the eight color maps shown in FIG. 4 shows the distribution of the absolute value of the amount of movement in the observation area. The position on the color map indicates the position in the observation area. It shows that the absolute value of the amount of movement is large. That is, a portion having a high color density indicates that it is pulsating vigorously (during contraction or relaxation). The arrows on the color map are drawn for the sake of explanation, and are not drawn on the actual color map.

  Of the eight color maps, the four color maps on the left are examples showing the propagation of pulsations after the administration of the organic solvent (control). The organic solvent basically does not affect the pulsation of the cultured cardiomyocytes 110. Examples of the organic solvent include dimethyl sulfoxide). Each of the four color maps shows, in order from the top, the pulsation immediately after administration (0 ms), after 40 ms has elapsed since administration, after 80 ms have elapsed since administration, and after 120 ms have elapsed since administration.

  The four color maps on the right side are examples showing the propagation of pulsation after administration of 1-heptanol. 1-heptanol is known to inhibit the function of a gap junction that relays signal transduction between cells. Each of the four color maps shows, in order from the top, pulsation immediately after administration (0 ms), after 80 ms from administration, after 160 ms from administration, and after 240 ms from administration.

  In the case of the left side of FIG. 4 (in the case of an example in which only an organic solvent is administered), as shown by the arrow, the pulsation (the dark portion of the color density) is expanded from the upper right side while expanding the range over time. Propagating linearly in the lower left direction away from the initial position. This shows that the cap junction functions normally and the propagation proceeds smoothly.

  On the other hand, in the case of the right side of FIG. 4 (in the case of an example in which 1-heptanol is administered), as indicated by the arrow, the pulsation (the portion having a high color density) is directed to rotate with the passage of time. Propagating in a curve while changing That is, it sometimes advances (reverses) in the direction of returning to the initial position. In addition, the pulsation takes a longer time to propagate than the left side (slow propagation speed). This indicates that the function of the gap junction is hindered and the propagation does not proceed smoothly.

  The color map in FIG. 5 compares pulsation propagation after administration of an organic solvent (control) and after administration of 18-β-Glycyrrhetinic acid. It is known that 18-β-glycyrrhetinic acid inhibits gap junctions like 1-heptanol. Each of the five color maps on the right side of FIG. 5 shows, in order from the top, pulsation immediately after administration (0 ms), after 80 ms from administration, after 120 ms from administration, after 160 ms from administration, and after 240 ms from administration. The state of is shown.

  In the case of the left side of FIG. 5 (in the case of an example in which only an organic solvent is administered), as indicated by the arrow, the pulsation (the portion having a high color density) is similar to the case of the left side of FIG. Propagating substantially linearly in the direction from top to bottom and away from the initial position. This shows that the cap junction functions normally and the propagation proceeds smoothly.

  On the other hand, in the case of the right side in FIG. 5 (in the case of an example in which 18-β-glycyrrhetinic acid is administered), as indicated by the arrows, the pulsation (the portion having a high color density) is from right to left and from the bottom. It propagates in various directions, such as from top to left and right. In addition, the propagation of pulsation may stop temporarily (no pulsation propagation occurs in the observation target region). In addition, the pulsation takes a longer time to propagate than the left side (slow propagation speed). This indicates that the function of the gap junction is hindered and the propagation does not proceed smoothly.

  The color map in FIG. 6 compares the state of pulsation propagation after administration of an organic solvent (control) and after administration of DL-sotalol. DL-sotalol is known to inhibit potassium channels. Each of the six color maps on the right side of FIG. 6 is, in order from the top, immediately after administration (0 ms), 40 ms after administration, 80 ms after administration, 120 ms after administration, 160 ms after administration, and after administration. The state of pulsation after 200 ms has been shown.

  In the case of the left side of FIG. 6 (in the case of an example in which only an organic solvent is administered), as in the case of the left side of FIG. 4 and FIG. As the time elapses, the light propagates substantially linearly in the direction from the upper left to the lower right so as to move away from the initial position. This shows that the pulsation of each cell is stable and the propagation proceeds smoothly.

  On the other hand, in the case of the right side of FIG. 6 (in the case where DL-sotalol is administered), as shown by the arrow, the pulsation (the portion having a high color density) propagates from the upper left to the lower right, but is observed. Within the region, the propagation stops. Thereafter, pulsation propagation from the lower left to the upper right starts. During the observation period, no pulsation occurs in a part of the area on the right side of the observation area. That is, the pulsation is not propagated to a partial region on the right side. Furthermore, the speed of pulsation propagation is slower than that on the left side.

  When DL-sotalol is administered, the relaxation process is changed by a change in potassium channel function that works in the relaxation process. As a result, the pulsation waveform of each cell varies, and the pulsation does not propagate smoothly as in the examples on the left side of FIGS.

  The evaluation unit 104 represents the absolute value of the motion amount of each block with such a two-dimensional color map. As shown in FIGS. 4 to 6, the evaluation unit 104 generates such a two-dimensional color map at a predetermined frame interval (may be every frame or every plural frames). That is, the evaluation unit 104 expresses the propagation of pulsation by the temporal change of the two-dimensional color map.

  The evaluation unit 104 can present this two-dimensional color map to the user as an image. That is, the drug evaluation device 100 can easily and non-invasively observe the state of pulsation propagation and present the observation result. The user can easily and non-invasively evaluate the influence (effect, toxicity, etc.) of the administered drug from the state of pulsation propagation in the presented image of the two-dimensional color map.

  The evaluation unit 104 can also quantitatively evaluate how the pulsation propagates using this two-dimensional color map. In the case of the example of FIG. 4, the state of propagation of pulsation after drug administration shown in the right map (state of linear propagation) is the state of propagation of pulsation before administration of drug shown in the left map ( This is different from the case of propagating to rotate in the observation area. For example, the evaluation unit 104 compares the state of propagation of pulsation before and after such drug administration, and whether or not the state of propagation of pulsation after drug administration is normal based on the magnitude of the difference value. Can be determined.

  Further, the evaluation unit 104 can determine whether or not the state of propagation of pulsation after drug administration is normal by detecting a change or direction (for example, reverse direction) of the propagation direction. Furthermore, the evaluation unit 104 can determine whether or not the state of propagation of pulsation after drug administration is normal by determining whether or not the propagation speed is sufficiently high.

  The evaluation unit 104 can output such an evaluation result as an evaluation value 114. That is, the drug evaluation apparatus 100 can easily and non-invasively observe the state of pulsation propagation, and can easily and non-invasively evaluate the evaluation target (the influence of the administered drug).

  Note that the drug evaluation device 100 may use an object other than the cultured cardiomyocytes 110 as an observation target. For example, cells other than cardiomyocytes may be the observation target, and other than the cells may be the observation target. However, it is desirable that the observation object be able to move itself and evaluate the drug administered to the observation object by evaluating the movement. Note that this movement may be autonomous (spontaneous) or may be based on an electric signal supplied from the outside.

[Evaluation index data generator]
FIG. 7 is a block diagram illustrating a main configuration example of the evaluation index data generation unit 103 in FIG. As illustrated in FIG. 7, the evaluation index data generation unit 103 includes a motion detection unit 121, a motion amount absolute value calculation unit 122, and a motion amount absolute value storage unit 123.

  The motion detection unit 121 receives the evaluation target image data 112 recorded from the evaluation target image data generation / recording unit 102, performs motion detection for each block, and uses the detection result (motion vector) as motion detection data. It supplies to the absolute value calculation part 122.

  The motion amount absolute value calculation unit 122 calculates a motion amount absolute value which is the size of each motion detection data (motion vector) supplied. The motion amount absolute value calculation unit 122 supplies the calculated motion amount absolute value to the motion amount absolute value storage unit 123 for storage.

  The motion amount absolute value storage unit 123 supplies the stored motion amount absolute value to the evaluation unit 104 as evaluation index data 113 at a predetermined timing or based on a request from the evaluation unit 104.

  The motion detection unit 121 to the motion amount absolute value storage unit 123 perform this process for each frame image of the evaluation target image data.

[Structure of image data to be evaluated]
FIG. 8 shows a structural example of the evaluation target image data 112 supplied to the evaluation index data generation unit 103. Imaging is performed in an evaluation section having a predetermined length (for example, T + 1 frame (T is an arbitrary natural number)). That is, the evaluation target image data 112 supplied to the evaluation index data generation unit 103 includes, for example, first to (T + 1) th frame image data 132-1 to 132- (T + 1) corresponding to the evaluation section.

[Configuration example of motion detection unit]
FIG. 9 is a block diagram illustrating a main configuration example of the motion detection unit 121. As illustrated in FIG. 9, the motion detection unit 121 includes a frame memory 141 and a motion vector calculation unit 142. The frame memory 141 holds frame image data 132 that is sequentially input as the evaluation target image data 112 for each frame period.

  The motion vector calculation unit 142 obtains the frame image data input as the evaluation target image data 112 at the current time and the frame image data at the next time (previous in time) held in the frame memory 141. input. Then, a motion vector indicating the motion between these two frame image data is calculated for each block. The calculated motion vector is supplied to the motion amount absolute value calculation unit 122 as motion detection data 151.

  The process executed by the motion detection unit 121 in FIG. 9 will be described in more detail. The motion vector calculation unit 142 receives the frame image data 132 at the current time and the frame image data 132 at the next (temporally previous) time. The motion vector calculation unit 142 divides the input frame image data 132 into M × N blocks 161 (M and N are arbitrary natural numbers), as shown in FIG. For example, motion detection is performed by a technique such as block matching between frame images to generate a motion vector. Each of the blocks 161 is composed of, for example, pixels of (16 × 16).

  The motion vector calculation unit 142 executes this motion detection processing by sequentially using the first to (T + 1) th frame image data 132. That is, the motion vector calculation unit 142 generates (M × N × T) motion detection data (motion vectors) using (T + 1) frame images. The motion vector calculation unit 142 supplies the motion vector calculated as described above to the motion amount absolute value calculation unit 122 as motion detection data.

  When the final motion detection process using the T-th and (T + 1) -th frame image data 132 is completed, the motion amount absolute value calculation unit 122, as shown in FIG. Motion detection data consisting of 171-1 to 171-T is supplied.

  Each of the frame unit motion detection data 171-1 to 171 -T moves with respect to the frame image data 132 at the current time obtained for each frame period and the frame image data 132 ahead (in time). It is obtained by performing the detection process.

  For example, the third frame unit motion detection data 171-3 includes the fourth frame image data 132-4 and the third frame image data 132-3 as frame image data at the current time and one time ahead, respectively. It can be obtained by inputting and performing motion detection.

  Each of the frame unit motion detection data 171-1 to 171-T is formed by (M × N) block unit motion detection data 181. Each block unit motion detection data 181 corresponds to one block 161, and is data indicating a motion vector detected for the corresponding block 161.

  As described above, the motion detection data 151 according to the present embodiment has a structure having (M × N) block unit motion detection data 181 for each frame unit motion detection data 171.

[Evaluation Department]
FIG. 12 is a block diagram illustrating a main configuration example of the evaluation unit 104. As illustrated in FIG. 12, the evaluation unit 104 includes a motion amount absolute value acquisition unit 201, a mapping unit 202, a temporal change analysis unit 203, a motion evaluation unit 204, a display unit 205, and an output unit 206.

  The motion amount absolute value acquisition unit 201 obtains the motion amount absolute value of the desired evaluation target image data 112 (for example, designated as an observation target by the user) from the motion amount absolute value storage unit 123 of the evaluation index data generation unit 103. Obtained as evaluation index data 113. The motion amount absolute value acquisition unit 201 supplies the acquired motion amount absolute value to the mapping unit 202.

  The mapping unit 202 maps the supplied motion amount absolute value on a plane according to the coordinates of the block, and generates a two-dimensional color map as shown in FIG. The mapping unit 202 generates the above-described two-dimensional color map for a plurality of frames (all or a part of the evaluation target image data 112).

  The mapping unit 202 supplies the generated two-dimensional color map to the display unit 205 to display the image, or supplies the generated two-dimensional color map to the output unit 206 to output the data to the outside of the drug evaluation apparatus 100 (another apparatus or the like). I will let you. The mapping unit 202 also supplies the generated two-dimensional color map to the temporal change analysis unit 203.

  Note that the mapping unit 202 only needs to generate information that can indicate the distribution of the motion amount absolute value, and the generated information is not limited to the two-dimensional color map. For example, it may be a three-dimensional or higher color map. Further, it may be a gray scale map instead of a color map. Furthermore, the mapping unit 202 may map the motion amount absolute value on the curved surface.

  The temporal change analysis unit 203 analyzes the temporal change (temporal change) of each supplied two-dimensional color map (motion amount absolute value distribution). For example, the temporal change analysis unit 203 sets a region (or point) having a predetermined feature in the two-dimensional color map as a region of interest (or point of interest), and obtains the temporal change thereof. The temporal change analysis unit 203 supplies each two-dimensional color map and the temporal change analysis result (for example, temporal change in the size, shape, position, etc. of the region of interest) to the motion evaluation unit 204.

  The motion evaluation unit 204 evaluates the motion amount distribution based on the supplied information. For example, the motion evaluation unit 204 evaluates the motion of the attention area. For example, the motion evaluation unit 204 determines whether there is a change in the route of the attention area before and after drug administration, determines whether there is an extreme change in the traveling direction of the attention area, It is determined whether or not the traveling speed changes. The motion evaluation unit 204 supplies such evaluation result data to the display unit 205 for display, or supplies it to the output unit 206 for output to the outside of the drug evaluation device 100 (such as another device). .

  The display unit 205 includes an arbitrary display device, images the two-dimensional color map supplied from the mapping unit 202, and displays the image on the display device. The display unit 205 images the evaluation result supplied from the motion evaluation unit 204 and displays the image on the display device.

  The output unit 206 has an arbitrary output interface, and outputs the two-dimensional color map data supplied from the mapping unit 202 to an external device or network of the drug evaluation apparatus 100 via the output interface. The output unit 206 also outputs the evaluation result data supplied from the motion evaluation unit 204 to an external device or network of the drug evaluation device 100 via the output interface.

[Motion evaluation part]
FIG. 13 is a block diagram illustrating a main configuration example of the motion evaluation unit 204 of FIG. As illustrated in FIG. 13, the motion evaluation unit 204 includes a non-moving region evaluation unit 211, a pulsation propagation velocity evaluation unit 212, a motion amount centroid evaluation unit 213, and a correlation histogram evaluation unit.

  The non-moving region evaluation unit 211 evaluates the number, area, or temporal change of regions where pulsation does not propagate (that is, regions where pulsation does not occur).

  After administration, there may be a region (non-pulsation region) that clearly does not move (does not pulsate) in the observation region. For example, in the case of FIG. 6, after administration of DL-sotalol, pulsation does not propagate to the right part of the observation region. That is, the pulsation is stopped.

  DL-sotalol inhibits potassium channels. When DL-sotalol is administered to cultured cardiomyocytes, the relaxation process changes due to a change in potassium channel function that works in the relaxation process, and the pulsation time (for example, action potential maintenance time) may be prolonged. In some cases, the pulsation itself may be stopped. Thus, cell movement may stop due to the toxicity of the drug.

  The number and area of such immobile regions (or their temporal changes) may be related to the toxicity of the administered drug. For example, in some cases, it can be evaluated that the toxicity of the drug is stronger as the number of immobile regions is larger or the area of the immobile regions is larger after administration. In some cases, the toxicity intensity of a drug can be evaluated by the time from immediately after administration until the immobile region increases, the time until the immobile region decreases, and the like thereafter.

  Therefore, for example, the immobilization area evaluation unit 211 uses the immobility area as an attention area, compares the attention areas in the two-dimensional color map before and after the administration, and compares the immobility area with the magnitude (change amount) of the difference. Evaluate number, size, position, shape, etc. Of course, the immovable region evaluation unit 211 can also compare the attention regions in the two-dimensional color map at a plurality of times after the medication. The immobility region evaluation unit 211 evaluates the toxicity and effect of the administered drug by evaluating the immobility region.

  The pulsation propagation speed evaluation unit 212 evaluates the pulsation propagation speed in the observation region or its temporal change.

  If the propagation of pulsation is hindered by the toxicity of the administered drug, the pulsation propagation speed may be affected. For example, when the pulsation time of each cell is extended, the pulsation propagation speed may change. That is, changes in pulsation propagation speed may be related to the toxicity of the administered drug. For example, in some cases, it can be evaluated that the toxicity of a drug is stronger as the reduction rate of the propagation speed of pulsation is greater after administration. In some cases, the toxicity intensity of a drug can be evaluated by the time from immediately after administration until the propagation speed is reduced, the time until the propagation speed is recovered thereafter, and the like.

  Therefore, for example, the pulsation propagation speed evaluation unit 212 sets the region of significant pulsation as the region of interest, compares the movement (speed) of the region of interest in the two-dimensional color map before and after the medication, Changes in the propagation speed of pulsations are evaluated based on the difference in the movement speed of the region (the amount of movement within a predetermined time). Of course, the pulsation propagation velocity evaluation unit 212 can also compare the movements of the region of interest in the two-dimensional color map at a plurality of times after medication. The pulsation propagation speed evaluation unit 212 evaluates the toxicity and effect of the administered drug by evaluating the pulsation propagation speed.

  The motion amount center of gravity evaluation unit 213 evaluates the position and locus of the center of gravity of the motion amount in the observation region.

  In general, when the pulsation propagates, the movement of each part in the observation region also changes, so that the position of the center of gravity of the movement amount in the observation region also changes. That is, the propagation of pulsation can be represented by the locus of the position of the center of gravity of the amount of movement. In other words, if the state of pulsation propagation (path, speed, etc.) changes due to the toxicity of the administered drug, it also affects the way the position of the center of gravity of the amount of movement changes.

  For example, as described with reference to FIGS. 4 to 6, a pulsation that has been linearly propagated in one direction before medication is propagated so as to rotate after medication, or is propagated in multiple directions. There is a case. For example, when a non-moving region is generated by medication, the propagation of pulsation may wrap around (rotate) around the non-moving region. Even if the immobilization region does not reach, if the pulsation cycle of each cell is biased between the regions, the propagation direction may change (rotate) depending on the bias.

  Furthermore, pulsation propagation may be divided into a plurality of directions in a non-moving region or the like. In cardiomyocytes, some cells play a role of pacemaking, and pulsation propagation to other cells is performed based on the pulsation of the cells. Due to the effects of drug administration, the cells that perform this pacemaking may be replaced with other cells. In some cases, the number of cells that perform pacemaking may increase or decrease. In that case, the pulsation propagation path changes significantly.

  In addition, propagation may stop midway. For example, pulsation propagation may be interrupted in the immobile region. Furthermore, the speed of propagation may change. For example, the propagation speed may change as the pulsation time of each cell extends.

  Due to such changes in propagation, pulsations may be propagated to the same region from different directions at different timings. In that case, the pulsation of each cell may be disturbed, and reentry may occur locally (may cause arrhythmia).

  Due to the change in pulsation propagation as described above, the locus of the center of gravity of the amount of movement also changes. Therefore, as shown in FIG. 14A, the motion amount centroid evaluation unit 213 divides the entire area of the two-dimensional color map into N small areas in the vertical direction and M small areas in the horizontal direction. The amount of motion v (m, n) is obtained every n). The motion amount center-of-gravity evaluation unit 213 calculates the coordinates (Gx, Gy) of the center of gravity of the motion as in the following formulas (1) and (2).

・・・（１）

・・・（２）

... (1)

... (2)

  When the coordinates of the center of gravity of the motion amount are obtained in this way for each two-dimensional color map, the motion amount center-of-gravity evaluation unit 213 determines the position of the center of gravity of each two-dimensional color map (each time) as shown in FIG. 14B. Plot on a two-dimensional map and draw the change (trajectory). The movement amount center of gravity evaluation unit 213 compares the locus of the center of gravity before and after the medication, and evaluates the change in the locus. Of course, the motion amount center of gravity evaluation unit 213 can also compare the locus of the center of gravity at a plurality of times after medication. The motion amount center-of-gravity evaluation unit 213 evaluates the toxicity and effect of the administered drug by evaluating the locus of the center of gravity of the motion amount.

  There may be a plurality of centroids for evaluating the trajectory. Further, the amount of movement of the center of gravity (the magnitude of pulsation) may be evaluated together. For example, the motion amount centroid evaluation unit 213 may plot the centroid of the motion amount on a three-dimensional map in which the position is represented by XY coordinates and the motion amount is represented by Z coordinates. The calculation method of the amount of motion of the center of gravity is arbitrary. For example, the obtained motion amount at the position of the center of gravity may be used as the amount of motion of the center of gravity, and the average value of the motion amounts in the vicinity of the center of gravity may be used as the amount of motion of the center of gravity. Further, the motion amount of the center of gravity may be calculated using the motion amount of the entire observation region.

  The correlation histogram evaluation unit 214 evaluates the motion distribution (speed, direction, etc.) within the observation region.

  In a normal state before administration, the cardiomyocytes repeat pulsation with a predetermined rhythm. Therefore, the motion distribution (speed, direction, etc.) in the observation region is substantially constant. If the state of propagation of pulsation changes as described above due to the toxicity of the administered drug after administration, the distribution of this movement will also change. Therefore, the correlation histogram evaluation unit 214 obtains a distribution (histogram) for the speed and direction of this movement before and after medication, and evaluates the change in the distribution to evaluate the toxicity and effect of the administered drug.

  A more specific example will be described. For example, the correlation histogram evaluation unit 214 calculates a pulsation correlation coefficient d between adjacent small regions, as shown in FIG. The correlation coefficient d is a parameter indicating a shift in pulsation timing as shown in the center of FIG. 15, and the value increases as the shift increases as shown in the right side of FIG. That is, the correlation coefficient d is the largest when the pulsation timings of both small regions are shifted by a half cycle. When the pulsation timings of the two small areas coincide, the value of the correlation coefficient d is 0.

As shown in FIG. 16A, the correlation histogram evaluation unit 214 calculates such a correlation coefficient d for each of the small areas adjacent to the small area to be processed in the vertical and horizontal directions (d _{0 to} d ₃ ). The correlation histogram evaluation unit 214 uses the correlation coefficient d (d _{0 to} d ₃ ), as shown in the following equations (3) and (4), the horizontal motion amount v _x and the vertical motion. The quantity v _y is calculated.

・・・（３）

・・・（４）

... (3)

... (4)

Correlation histogram evaluation section 214, and a their motion amount v _x and the amount of movement v _y, as shown in FIG. 16B, the small region to be processed (m, n) the amount of movement v (m, n), The direction θ (m, n) is obtained. The correlation histogram evaluation unit 214 obtains the amount of motion and its direction in this way for each small region, and generates a motion amount (speed) and direction histogram (frequency distribution) as shown in FIG.

  FIG. 17A shows a histogram of movement speed and direction before drug administration, and FIG. 17B shows a histogram of movement speed and direction after drug administration. As shown in FIG. 17A and FIG. 17B, when these distributions are different before and after medication, it can be determined that there is an influence due to drug administration. That is, the correlation histogram evaluation unit 214 evaluates the toxicity and effect of the administered drug by obtaining a distribution (histogram) for the speed and direction of this movement before and after the medication and evaluating the change in the distribution. .

  The immovable region evaluation unit 211 to the correlation histogram evaluation unit 214 supply the obtained evaluation results to the evaluation result data generation unit 215, respectively. The evaluation result data generation unit 215 appropriately summarizes each evaluation result and supplies it as evaluation result data to the display unit 205 and the output unit 206 (FIG. 12).

  The configuration of the motion evaluation unit 204 described above is an example. The motion evaluation unit 204 can have an arbitrary configuration, and can evaluate an arbitrary index as long as it relates to the motion of the observation target.

  As described above, the drug evaluation apparatus 100 easily and non-invasively observes the state of propagation of pulsation of the cultured cardiomyocytes 110, and easily and non-invasively evaluates an evaluation target (effect of the administered drug). be able to.

[Flow of evaluation process]
Next, an example of the flow of evaluation processing executed by the drug evaluation device 100 will be described with reference to the flowchart of FIG.

  When the evaluation process is started, the imaging unit 101 of the drug evaluation device 100 images the cultured cardiomyocytes 110 that are the observation target in step S101. In step S102, the evaluation target image data generation / recording unit 102 generates evaluation target image data 112 from the image signal 111 obtained by imaging in step S101.

  In step S103, the evaluation index data generation unit 103 performs motion detection using the evaluation target image data 112 generated in step S102, calculates a motion amount absolute value, and generates evaluation index data 113. In step S104, the evaluation unit 104 generates a two-dimensional color map using the evaluation index data 113 generated in step S103, and calculates an evaluation value 114.

  In step S105, the evaluation unit 104 outputs the evaluation value 114 calculated in step S104, and ends the evaluation process.

[Flow of evaluation index data generation processing]
Next, an example of the flow of the evaluation index data generation process executed in step S103 of FIG. 18 will be described with reference to the flowchart of FIG.

  When the evaluation index data generation process is started, the motion detection unit 121 of the evaluation index data generation unit 103 detects a motion to be evaluated for each block and generates a motion vector in step S121. In step S122, the motion amount absolute value calculation unit 122 calculates the motion amount absolute value of the motion vector of each block generated in step S121.

  In step S123, the motion amount absolute value storage unit 123 stores the motion amount absolute value calculated in step S122.

  In step S124, the motion detection unit 121 determines whether or not data for a predetermined period (evaluation section) has been processed. When it is determined that there is a frame image for which motion detection has not been performed in the predetermined evaluation section, the motion detection unit 121 returns the process to step S121 and repeats motion detection for a new processing target frame image.

  If it is determined in step S124 that motion detection has been performed on all the frame images to be processed in the predetermined evaluation section, the evaluation index data generation process ends, the process returns to FIG. 18, and the process proceeds to step S104. To proceed.

[Flow of correlation evaluation process]
Next, an example of the flow of the impact evaluation process executed in step S104 in FIG. 18 will be described with reference to the flowchart in FIG.

  When the influence evaluation process is started, the motion amount absolute value acquisition unit 201 acquires the motion amount absolute value from the motion amount absolute value storage unit 123 in step S141.

  In step S142, the mapping unit 202 creates a two-dimensional color map by mapping the motion amount absolute value acquired in step S141 on a plane.

  In step S143, the temporal change analysis unit 203 analyzes the temporal change of the two-dimensional color map in each two-dimensional color map of the motion amount absolute value created in step S142.

  In step S144, the motion evaluation unit 204 evaluates temporal changes (motions between the two-dimensional color maps) of the two-dimensional color map analyzed in step S143. That is, the motion evaluation unit 204 evaluates the influence of drug administration. The motion evaluation unit 204 displays the evaluation value 114 on the display unit 205 or outputs the evaluation value 114 to the outside of the medicine evaluation apparatus 100 via the output unit 206.

  When the process of step S144 ends, the motion evaluation unit 204 ends the impact evaluation process and returns the process to FIG.

[Flow of motion evaluation process]
Next, an example of the flow of the motion evaluation process executed in step S144 of FIG. 20 will be described with reference to the flowchart of FIG.

  When the motion evaluation process is started, in step S161, the non-moving area evaluation unit 211 evaluates the non-moving area. In step S162, the pulsation propagation speed evaluation unit 212 evaluates the pulsation propagation speed. In step S163, the motion amount center of gravity evaluation unit 213 evaluates the center of gravity of the motion amount. In step S164, the correlation histogram evaluation unit 214 evaluates the speed and direction of pulsation propagation using a histogram. In step S165, the evaluation result data generation unit 215 generates evaluation result data for output or display.

  When the process of step S165 ends, the evaluation result data generation unit 215 ends the motion evaluation process and returns the process to FIG.

  As described above, by performing various processes, the drug evaluation apparatus 100 can easily and noninvasively observe the observation target, and the influence of the drug administration on the cultured cardiomyocytes 110 can be more easily and noninvasively performed. Can be evaluated.

  In other words, in the case of this technology, since special culture dishes and fluorescent reagents are not required, changes in cell pulsation behavior can be captured easily, non-invasively and inexpensively, and drug toxicity etc. can be evaluated easily and accurately. Can do. It is also suitable for automation.

  In general, the toxicity of drugs can be broadly divided into short-term toxicity that appears in a short period of several seconds to several minutes after administration, and after a long period of time from several hours to several days after administration. Has long-term toxicity. When a fluorescent reagent or an electrode is used, it may be unsuitable for long-term toxicity observation because it affects the observation target. On the other hand, in the case of the present technology, the observation target can be observed non-invasively. In the case of the present technology, long-term toxicity can be easily observed by the same method as that for observing short-term toxicity. Therefore, this technique is suitable not only for observation of short-term toxicity but also for observation of long-term toxicity.

  Moreover, since this technique can perform observation of short-term toxicity and observation of long-term toxicity in the same manner as each other, long-term observation such as several days can be performed immediately after dosing. That is, the present technology can also observe and evaluate the change in toxicity over time.

  In addition, when the cultured cells to be observed grow and become dense, staining with a fluorescent reagent is generally difficult. However, in the case of this technology, the observation target can be observed non-invasively. Regardless of the degree of growth, observation and evaluation can be performed stably.

  By the way, the pulsation of cardiomyocytes is composed of contraction and relaxation. In general, the relaxation of the myocardium corresponds to the T wave as referred to in the electrocardiogram, and corresponds to the repolarization of the myocardial cell membrane. This extension of the T wave is generally called QT extension as an extension of the time between the Q wave and the T wave. If this symptom appears, the possibility of arrhythmia is pointed out. For example, such QT prolongation occurs when the drug administered to the cultured cardiomyocytes inhibits the ion channel into and out of the potassium channel. For example, DL-sotalol is known to inhibit potassium channels. That is, when DL-sotalol is administered to cultured cardiomyocytes, the relaxation process changes due to a change in potassium channel function that works in the relaxation process.

  However, in reality, even when QT prolongation occurs, for example, when substantially uniform QT prolongation occurs in the entire myocardial cell, there is no arrhythmia because there is no significant pulsation shift between cells. It is also possible. Conversely, if the gap junction is inhibited as described above, an arrhythmia may occur even if QT prolongation does not occur. In the case of the present technology, since the propagation of pulsation can be observed easily and non-invasively, the occurrence of arrhythmia can be detected regardless of the occurrence of such QT prolongation.

  In the case of the present technology, the observation area may be a relatively narrow range, for example, about 0.6 mm square, and the test can be performed with a small number of cells and a small reagent. In addition, it can be sufficiently evaluated by a commercially available high-density culture plate (1536-well plate (1.7 mm diameter / 1 well) and 384-well plate (3.6 mm diameter / 1 well). It is also suitable for initial screening, and in the case of the present technology, observation is possible by the same method regardless of the width of the observation range, so that it is possible to easily cope with changes in the observation range.

  Furthermore, research is ongoing on methods for evaluating the toxicity of drugs, and new evaluation methods and evaluation criteria may be proposed in the future. In the case of the present technology, since the state of the observation target can be observed non-invasively, application to more various evaluation methods and evaluation standards is easy.

  Furthermore, the present technology can be applied to any device that can be evaluated by observing the cultured cardiomyocytes 110. For example, it may be a gas, a liquid, or a solid. Moreover, environmental conditions at the time of observation (for example, temperature, humidity, atmospheric pressure, brightness, vibration, magnetic field, etc.) may be used.

  In addition, since this technology can easily observe the propagation of pulsation, the pulsation rhythm of the cell is detected by inserting a fluorescent dye and detecting the calcium concentration that fluctuates due to the excitation (action potential) of the cell. It can also be applied to a method for evaluating information propagation patterns of cells.

<2. Second Embodiment>
[Personal computer]
The series of processes described above can be executed by hardware or can be executed by software. In this case, for example, a personal computer as shown in FIG. 22 may be configured.

  In FIG. 22, a CPU (Central Processing Unit) 301 of the personal computer 300 performs various processes according to a program stored in a ROM (Read Only Memory) 302 or a program loaded from a storage unit 313 to a RAM (Random Access Memory) 303. Execute the process. The RAM 303 also appropriately stores data necessary for the CPU 301 to execute various processes.

  The CPU 301, ROM 302, and RAM 303 are connected to each other via a bus 304. An input / output interface 310 is also connected to the bus 304.

  The input / output interface 310 includes an input unit 311 including a keyboard and a mouse, a display including a CRT (Cathode Ray Tube) and an LCD (Liquid Crystal Display), an output unit 312 including a speaker, and a hard disk. A communication unit 314 including a storage unit 313 and a modem is connected. The communication unit 314 performs communication processing via a network including the Internet.

  A drive 315 is connected to the input / output interface 310 as necessary, and a removable medium 321 such as a magnetic disk, an optical disk, a magneto-optical disk, or a semiconductor memory is appropriately mounted, and a computer program read from them is It is installed in the storage unit 313 as necessary.

  When the above-described series of processing is executed by software, a program constituting the software is installed from a network or a recording medium.

  For example, as shown in FIG. 22, the recording medium is distributed to distribute the program to the user separately from the apparatus main body, and includes a magnetic disk (including a flexible disk) on which the program is recorded, an optical disk ( It is only composed of removable media 321 consisting of CD-ROM (compact disc-read only memory), DVD (including digital versatile disc), magneto-optical disc (including MD (mini disc)), or semiconductor memory. Rather, it is composed of a ROM 302 on which a program is recorded and a hard disk included in the storage unit 313, which are distributed to the user in a state of being incorporated in the apparatus main body in advance.

  The program executed by the computer may be a program that is processed in time series in the order described in this specification, or in parallel or at a necessary timing such as when a call is made. It may be a program for processing.

  Further, in the present specification, the step of describing the program recorded on the recording medium is not limited to the processing performed in chronological order according to the described order, but may be performed in parallel or It also includes processes that are executed individually.

  Further, in this specification, the system represents the entire apparatus composed of a plurality of devices (apparatuses).

  In addition, in the above description, the configuration described as one device (or processing unit) may be divided and configured as a plurality of devices (or processing units). Conversely, the configurations described above as a plurality of devices (or processing units) may be combined into a single device (or processing unit). Of course, a configuration other than that described above may be added to the configuration of each device (or each processing unit). Furthermore, if the configuration and operation of the entire system are substantially the same, a part of the configuration of a certain device (or processing unit) may be included in the configuration of another device (or other processing unit). . That is, the present technology is not limited to the above-described embodiment, and various modifications can be made without departing from the gist of the present technology.

In addition, this technique can also take the following structures.
(1) a motion detection unit that detects the motion of the observation target for each partial region of the observation region;
A motion amount calculation unit for calculating a motion amount of each motion detected by the motion detection unit;
An image processing apparatus comprising: a map creation unit that creates a map representing a position and a size of each motion amount calculated by the motion amount calculation unit.
(2) The motion detection unit detects the motion for each frame of the moving image to be observed,
The image processing apparatus according to (1), wherein the map creation unit creates the map for each frame of the moving image to be observed.
(3) The image processing device according to (2), further including: a motion evaluation unit that evaluates a distribution of a motion amount between each map created by the map creation unit.
(4) The image processing apparatus according to (3), wherein the observation target is a cardiomyocyte.
(5) The image processing device according to (4), wherein the motion evaluation unit evaluates at least one of the direction, speed, rotation, stop, and change with time of the pulsation propagation.
(6) The image processing apparatus according to (5), wherein the motion evaluation unit evaluates the state of pulsation propagation after medication.
(7) The image processing device according to any one of (4) to (6), wherein the motion evaluation unit evaluates a region that does not beat.
(8) The image processing device according to any one of (4) to (7), wherein the motion evaluation unit evaluates a change in pulsation propagation speed.
(9) The image processing device according to any one of (4) to (8), wherein the motion evaluation unit evaluates a locus of the center of gravity of the motion amount for each map.
(10) The image processing device according to any one of (4) to (9), wherein the motion evaluation unit evaluates the speed and direction of the pulsation propagation using a histogram.
(11) The image processing apparatus according to any one of (3) to (10), further including a display unit that displays a result of the evaluation by the motion evaluation unit.
(12) The image processing apparatus according to any one of (3) to (11), further including an output unit that outputs a result of the evaluation by the motion evaluation unit.
(13) The image processing apparatus according to any one of (1) to (12), further including a display unit that displays an image of the map.
(14) The image processing apparatus according to any one of (1) to (13), further including an output unit that outputs data of the map.
(15) An image processing method for an image processing apparatus,
The motion detector detects the motion of the observation target for each partial area of the observation area,
The motion amount calculation unit calculates the motion amount of each detected motion,
An image processing method in which a map creation unit creates a map representing the position and size of each calculated motion amount.
(16)
A motion detector that detects the motion of the observation target for each partial region of the observation region;
A motion amount calculation unit for calculating a motion amount of each detected motion;
A computer-readable recording medium recording a program for functioning as a map creation unit that creates a map representing the position and size of each calculated motion amount.
(17) Connect the computer
A motion detector that detects the motion of the observation target for each partial region of the observation region;
A motion amount calculation unit for calculating a motion amount of each detected motion;
A program for functioning as a map creation unit that creates a map representing the position and size of each calculated amount of motion.

  DESCRIPTION OF SYMBOLS 100 Drug evaluation apparatus, 101 Imaging part, 102 Evaluation object image data generation recording part, 103 Evaluation index data generation part, 104 Evaluation part, 121 Motion calculation part, 122 Motion amount absolute value calculation part, 123 Motion amount absolute value storage part, 141 frame memory, 142 motion vector calculation unit, 201 motion amount absolute value acquisition unit, 202 mapping unit, 203 temporal change analysis unit, 204 motion evaluation unit, 205 display unit, 206 output unit

Claims (14)

An image processing apparatus comprising: a generation unit that determines a movement amount or direction of cardiomyocytes for each partial region of an observation region, and generates a distribution of the determined movement amount or direction of the cardiomyocytes for each partial region. The image processing apparatus according to claim 1, wherein the generation unit displays a distribution regarding a movement amount or direction of the cardiomyocytes for each of the determined partial regions. The image processing apparatus according to claim 1, wherein the generation unit displays a frequency distribution with respect to a movement amount or direction of the cardiomyocytes for each of the determined partial regions. The image processing apparatus according to claim 1, wherein the generation unit displays the distribution before and after drug administration. The image processing apparatus according to claim 1, further comprising: an evaluation unit that evaluates propagation of movement of the cardiomyocytes based on the change in the distribution. The image processing apparatus according to claim 5, wherein the evaluation unit evaluates a change in the distribution before and after drug administration. The image processing apparatus according to claim 6, wherein the evaluation unit evaluates toxicity or effect of the administered drug. The image processing apparatus according to claim 5, wherein the evaluation unit evaluates propagation of pulsation of cardiomyocytes. The image processing apparatus according to claim 1 , wherein the partial area constitutes the whole or part of the observation area . The image processing apparatus according to claim 1 , wherein the generation unit displays a distribution regarding a movement amount and a direction of the cardiomyocytes for each of the determined partial regions . A motion detector that detects the movement of the cardiomyocytes for each of the partial regions of the observation region;
A motion calculator that calculates the amount or direction of motion of the cardiomyocytes detected by the motion detector;
The image processing apparatus according to claim 1 , further comprising: The motion detection unit detects the motion for each frame of the moving image of the cardiomyocytes,
The motion calculation unit calculates the motion amount or direction for each frame of the moving image of the cardiomyocytes.
The image processing apparatus according to 請 Motomeko 11. A motion amount or direction of cardiomyocytes is determined for each partial region of the observation region, and a distribution of the determined amount or direction of the cardiomyocytes for each of the determined partial regions is generated
Image processing method. Computer
Generating unit determines a motion amount or direction of cardiomyocytes in each partial area of the viewing area, to produce a distribution of the motion amount or direction of the myocardial cells of each of the partial region determined
Program to function as.

Images